Selective upregulation of arterial endothelial nitric oxide
synthase in pulmonary hypertension.
Resta, Thomas C., Rayna J. Gonzales, William G. Dail, Thomas C.
Sanders, and Benjimen R. Walker.
Departments of Physiology and Anatomy, University of New Mexico
School of Medicine, Albuquerque, New Mexico 87131
APStracts 3:0401H, 1996.
We have previously demonstrated that arterial, but not venous,
vasodilatory responses to endothelium-derived nitric oxide (EDNO)
-dependent agonists are enhanced in lungs isolated from rats with
chronic hypoxia (CH)-induced pulmonary arterial hypertension. These
data suggest that CH is associated with increased endothelial nitric
oxide synthase (eNOS) activity within the pulmonary arterial
vasculature. In addition, the correlation of increased pulmonary
arterial pressure with selectively enhanced arterial responsiveness
to EDNO-mediated agonists suggests that arterial hypertension, rather
than hypoxia per se, is a contributing factor in this response.
Therefore, we hypothesized that 1) CH selectively upregulates eNOS
within the pulmonary arterial vasculature, and 2) monocrotaline (MC)
-induced pulmonary arterial hypertension selectively enhances
pulmonary arterial dilation to EDNO-dependent dilators and
upregulates arterial eNOS. We examined responses to the EDNO
-dependent dilators arginine vasopressin (AVP) and ionomycin in U
-46619-constricted, isolated perfused lungs from control and MC
-treated rats. Microvascular pressure was assessed by double occlusion
technique, allowing calculation of segmental resistances. Lungs from
MC-treated rats exhibited augmented arterial dilation to AVP compared
to controls. However, responses to ionomycin were not different
between the two groups. Quantitative immunocytochemistry was used to
compare pulmonary eNOS immunoreactivity in vessels from control, CH,
and MC-treated rats. eNOS staining was more intense in arteries of CH
and MC-treated rats compared to those of control animals, whereas CH
and MC-treatment had no effect on eNOS staining in veins. We conclude
that pulmonary arterial hypertension, or some factor associated with
hypertension, may be responsible for the augmented EDNO-dependent
arterial dilation and upregulation of arterial eNOS in lungs from CH
and MC-treated rats.
Received 13 June 1996; accepted in final form 4 September 1996.
APS Manuscript Number H523-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996